ATP13A2激活酸通路,通过TFEB-PGD轴促进结直肠癌的生长
Fan Zhang1, Zhiwei Wu1, Bowen Yu1
1Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, China.
Clinical and translational medicine
|May 27, 2023
概括
酸 (PPP) 途径驱动着结直肠癌 (CRC) 的生长. ATP13A2通过增加糖酸脱酶 (PGD) 转录来激活PPP,使其成为CRC的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 酸通路 (PPP) 对于瘤细胞在压力下生存和增殖至关重要.
- PPP在结直肠癌 (CRC) 病原发生中的特定作用尚未完全理解.
研究的目的:
- 研究PPP在结直肠癌 (CRC) 中的作用.
- 为了确定调节CRC中PPP的新型基因.
- 探索ATP13A2作为CRC的潜在治疗点.
主要方法:
- 使用TCGA和GEO数据库进行基因表达分析.
- 在体外测试以评估细胞增殖和氧化应激.
- 染色体免疫沉和双化酶试验以阐明分子机制.
- 在体内研究使用患者衍生的异种移植 (PDX),器官 (PDO) 和AOM/DSS模型.
主要成果:
- ATP13A2被确定为一种新型基因,可以调节CRC中的PPP.
- 缺少ATP13A2抑制了CRC生长和PPP活动,增加了活性氧物种.
- 通过促进TFEB核局部化和PGD转录,ATP13A2过度表达增强了CRC生长和PPP活动.
- 在临床前模型中,ATP13A2倒置抑制了CRC生长.
结论:
- ATP13A2通过通过TFEB脱化来增强PGD转录来激活CRC中的PPP.
- ATP13A2在CRC进展中发挥着重要作用,并代表着潜在的治疗点.
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